• The Human microbiome as a therapeutic target for metabolic diseases and the role of gut microbiome metabolites in obesity, A Review
  • Parvin Mohammadshafiei,1,*
    1. Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Iran


  • Introduction: The human body is host to a vast number of microbes, including bacterial, fungal, and protozoal microorganisms, which together constitute our microbiota. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders. The human microbiome resides in our gastrointestinal tract and creates a dynamic and complex microbial ecosystem of more than 1000 microbial species and their phages. Based on epidemiological and omics studies combined with in vitro studies using various cell models and in vivo studies in mice, human health and disease risk may be mediated by the human microbiome. In adult life, these microbes are mainly influenced by lifestyle, medication, and host genetics. The gut microbiota, in turn, produce microbial components that act not only on local cells in the gut but also on peripheral tissues via systemic circulation, playing a crucial role in training our immune system and regulating gut endocrine function and neurological signaling. They are also involved in modifying drug action and metabolism, eliminating toxins, and producing numerous signaling compounds. There is an increasing global prevalence of metabolic diseases associated with un- healthy lifestyles. These include type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), hypertension, hyperlipidemia, and obesity. Evidence shows that the intestinal microbiome is intrinsically linked with overall health, including obesity risk. Obesity and obesity-related metabolic disorders are characterized by specific alterations in the composition and function of the human gut microbiome. Mechanistic studies have indicated that the gastrointestinal microbiota can influence both sides of the energy balance equation; namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Moreover, its composition is not fixed and can be influenced by several dietary components. This fact raises the attractive possibility that manipulating the gut microbiota could facilitate weight loss or prevent obesity in humans. Emerging as possible strategies for obesity prevention and/or treatment are targeting the microbiota, to restore or modulate its composition through the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics), or both (synbiotics), or even fecal transplants. Despite the wide variation in the pathologies of these common metabolic disorders, they are all associated with abnormalities in the composition and function of the human microbiota. It remains questionable whether there is a causal relationship between host metabolism and the microbiome. To date, results obtained from animal and fecal microbiota transplantation studies have demonstrated causal effects of the microbiome on host health. Importantly, recent developments in next-generation microbiome sequencing to obtain comprehensive gene catalogs combined with targeted bioinformatics have provided a substantial amount of new knowledge on the role of the gut microbiota. This review will discuss the potential use of the human microbiome as a therapeutic target to improve host metabolism.
  • Methods: This study reviews data accumulated from literature and prestigious case studies that are in connection with our subject. The search words were:" Human microbiota,” “Microbial metabolites,” “metabolic disease,” “Short-chain fatty acid,” Microbiome”, “gut microbiome,” Metabolism ”, ” Obesity” using PubMed, Scopus, Science Direct, and Google Scholar databases. Furthermore, manual searches of other relevant journals and keyword searches were performed. We have focused on published papers from 2010 to 2024.
  • Results: Several studies have identified potential causal associations between gut microbiota and metabolic disorders, and obesity as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported.
  • Conclusion: A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders.
  • Keywords: Gut microbiota, Microbial metabolites, Obesity, Microbiome, metabolic disease